a Robert Baran, MD, b Frederique Anne Le Gal, MD, PhD, a Stephane Dalle, MD, c Sandra Ronger, MD, c Roberta Pandolfi, MD, c Olivier Gaide, MD, a Lars Einar French, MD, a Paul Laugier, MD, a Jean Hilaire Saurat, MD, a Ashfaq Ahmed Marghoob, MD, d and Luc Thomas, MD, PhD c Geneva, Switzerland; Cannes and Lyon, France; and New York, New York Longitudinal pigmentation of the nail is very common. The differential diagnosis varies from subungual hematoma, to a fungal infection, to a melanocytic lesion (lentigo, nevus melanoma, etc.) to others. Often, dermatologists do not feel at ease with these pathologies and management is often not clear. In many cases, a biopsy is not helpful because an inadequate technique was chosen. The use of noninvasive techniques such as dermoscopy has been described to be useful for the preoperative evaluation and the management decision. Using these technique, one will be able to reduce the number of unnecessary surgeries and to choose the most adequate biopsy technique. In this article, we will review the management, including diagnosis as well as differential diagnosis of nail pigmentations and propose a new algorithm for the non invasive diagnosis of nail pigmentation. ( J Am Acad Dermatol 2007;56:835-47.) L ongitudinal pigmentation of the nail is a common presenting problem in general der- matology. The differential diagnosis varies from subungual hematoma to a fungal infection to a melanocytic lesion (ie, lentigo, nevus, melanoma) among others. 1 Dermatologists are often unsure regarding their clinical diagnosis and lack confidence in managing this condition. Furthermore, many physicians are also reluctant to perform biopsies of the nail matrix because the procedure is painful and can result in permanent nail dystrophy. To compli- cate matters, when a decision to biopsy is finally rendered it is not uncommon for inadequate biopsy specimens (eg, biopsy specimen of the nail plate instead of the nail matrix) to be submitted to the pathologist. This in turn compromises the ability of the pathologist to render an accurate diagnosis. Fortunately, the use of noninvasive techniques such as dermoscopy can assist clinicians in correctly evaluating and diagnosing nail pigmentation. 1 This in turn will reduce the number of unnecessary surgeries while helping physicians determine the most appropriate biopsy technique and site of biopsy if it were deemed necessary to biopsy. In this article, we will review diagnosis and management of nail pigmentation and propose a new algorithm for the noninvasive diagnosis of nail pigmentation using dermoscopy. We will describe and review the most common biopsy techniques and the management of melanoma of the nail matrix. PRACTICAL APPROACH Personal history The physician should try and elicit a history as to whether the pigment was present since birth or acquired. Furthermore, the history of its duration, history of what made the patient rst become aware of it, and whether the patient has observed any change in the nail lesion may provide clues for the correct diagnosis. Many patients nd it difcult to verbally describe what the nail looked like and how it had changed over time. To overcome this problem we have found it useful to allow the patient to draw their impression of what the lesion initially looked like and to draw the perceived change on a simple schematic of a nail. Specic questions pertaining to athletic activities, recent trauma, physical exertion such as long hiking trips, or the use of blood thinners such as aspirin and warfarin may help in differentiating subungual hem- orrhage fromother causes of nail pigment. Obtaining a thorough history of any medications the patient is ingesting may help identify drugs that may contrib- ute to abnormal nail pigmentation. 2,3 Clinical examination A complete examination must include the inspec- tion of all 20 nails, periungual skin, and the oral From the Pigmented Skin Lesion Unit, Department of Dermatol- ogy, University Hospital Geneva a ; Nail Disease Center, Cannes b ; and Departments of Dermatology at Ho tel Dieu, Lyon, c and Memorial Sloan Kettering Cancer Center, New York. d Funding sources: None. Conflicts of interest: None declared. Reprint requests : Ralph P. Braun, MD, Department of Dermatology, University Hospital Geneva, 24, rue Micheli-du-Crest, CHe1211 Geneva 14, Switzerland. E-mail: braun@melanoma.ch. Published online March 6, 2007. 0190-9622/$32.00 2007 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2006.12.021 835 mucosa. Examination of the oral and genital mucosa can aid in correctly identifying Peutz-Jeghers syn- drome 4 or the Laugier Hunziker syndrome. 5-8 The clinician should record the diameter of the pigmentation at both the distal and proximal ends of the nail. In addition, the color or colors and whether the lesion has an overall homogeneous or heteroge- neous appearance should be recorded. Dermoscopy examination Dermoscopy is a noninvasive method that helps to narrow the differential diagnosis of pigmented lesions of the skin and can assist in the recognition of early melanoma. 9,10 It has been shown that dermo- scopy increases the diagnostic accuracy compared with clinical visual inspection. Dermoscopy uses an immersion technique to render the stratum corneum translucent. It also provides optical magnification. 11 Handheld devices called dermoscopes are easy to use, and relatively inexpensive. Recently, dermo- scopy has been described to be useful for the evaluation and diagnosis of longitudinal melanony- chia. 1,12 For the examination of the nail apparatus we recommend the use of a gel such as ultrasound gel as immersion medium 11 because its decreased viscosity permits it to stay on the nail plate and fill any concavities without rolling off. For the evaluation of the pigmentation and to appreciate the thin lines within the nail band, it is useful to vary the focus of the device during the examination. The following criteria can be evaluated by dermoscopy. 1 Gray pigmented band composed of multiple thin homogeneous grayish lines. This pattern is usually a result of epithelial hyperpigmentation without accompanying melanocytic hyperplasia such as is seen in a lentigo, drug-induced pigmen- tation, and ethnic pigmentation. Brown pigmented band. The brown pig- mented band is usually composed of multiple thin brown lines. These lines can be regular or irregular and are caused by melanocytic hyperplasia as seen in a nevus or melanoma. There are two main patterns seen within brown pigmented bands. Regular pattern: Brown longitudinal parallel lines with regular spacing and thickness. This pat- tern is usually associated with a brown homogenous color of the background band. The color of the individual lines within the band can vary from light brown to black. However, within any given band, the lines will be composed of similar shades of brown throughout the lesion. The spacing between the lines is regular and the thickness of the lines is relatively uniform throughout the band. The lines comprising the band are oriented parallel to each other. Irregular pattern: The band comprises multiple longitudinal brown to black lines with irregular spacing and thickness and disruption of parallelism. This pattern is also associated with a homogeneous brown pigmentation of the back- ground nail band. However, the color of the indi- vidual lines varies from light brown to black. In fact it is common to observe many different colored lines within the nail band. The lines vary in their thickness and spacing. These lines, normally arranged parallel to each other, can lose their parallelism and cross into each other. Dermoscopy of the free edge of the nail Apart from the examination of the nail plate, perionychium, and hyponychium, dermoscopy can also be used to examine the free edge of the nail plate. Examination of the free edge of the nail plate can help determine whether the origin of the pig- mentation is from the proximal or distal nail matrix. 13 As a result of the natural growth of the nail, pigment produced in the proximal nail matrix will be incor- porated into the upper portion of the nail plate and pigment produced in the distal nail matrix will appear in the lower part of the nail plate. 14 Thus, when examining the free edge of the nail plate particular attention should be placed on determining whether the pigment is located in the upper or lower portion the nail plate. This information, in turn, will help isolate which part of the matrix may need to be biopsied. If doubt exists as to the origin of the pigment one can always obtain a nail clipping and stain it with Fontana-Masson stain. This will help determine the location of melanin within the nail plate, which in turn will help determine whether the pigment originated in the proximal or distal nail matrix. DIFFERENTIAL DIAGNOSIS OF NAIL PIGMENTATION The rst and most important task necessary to diagnose the cause of nail pigmentation is to differ- entiate whether the pigment is of melanocytic or nonmelanocytic origin. 2 In most cases this task can be accomplished by clinical inspection and exami- nation with dermoscopy. In nonmelanocytic lesions such as fungal infections or subungual hematoma, the pigment tends to be distributed homogenously. In melanocytic lesions, the melanin is found in cellular inclusions, 10 which can be easily identified as small granules less than 0.1 mm in diameter under dermoscopy. Thus, if such granules are detected under dermoscopy, the lesion should be considered to be of melanocytic origin. A summary of the causes of nail pigmentation is shown in Table I. J AM ACAD DERMATOL MAY 2007 836 Braun et al Nail pigment of nonmelanocytic origin (nail hyperchromia) Exogenous pigmentation. There are multiple causes that can lead to exogenous nail pigment. Among the most frequent causes are contact with chemical agents, topical application of therapeutic agents such as silver nitrate or ethacridinlactat, tobacco, and cosmetics such as henna and hair dyes. 14-16 Subungual hematoma. Subungual hematoma usually appears as a reddish to reddish-black pig- ment depending on the age of the bleed. Dermo- scopically one is usually able to identify small reddish to reddish-black globules along the proximal and lateral margins of the pigment (Fig 1). The distal part will often have streaks of pigment. The pigment is homogenous and no melanin granules can be observed. The hematoma will progressively grow out distally as the nail plate grows. It is important to remember that a subungual hematoma can on rare occasions be caused by an episode of hemorrhage or caused by neovascularization within a tumor and, thus, the presence of subungual blood should not be used to rule out the diagnosis of melanoma. Hence, any subungual hemorrhage that does not grow out with the nail or that recurs at the same place requires special attention and further examination including radiograph of the distal phalange to exclude exostosis. If the diagnosis cannot be determined by radiologic studies then the lesion should be biopsied. Fungal or bacterial infection. Nails infected with Trichophyton rubrum (var nigricans) or with dermatiaceous fungi such as Scytalidium dimidia- tumare pigmented (Fig 2). Although difficult to treat, the pigmentation will fade after successful treatment. Nail pigmentation of melanocytic origin As mentioned earlier, melanonychia striata will reveal tiny melanin granules in the nail plate under dermoscopy. Fig 3 shows melanin inclusions of the nail plate at high magnification. Nail pigmentation caused by epithelial hyperpigmentation. The dermoscopy correlate of epithelial hyperpigmentation is the presence of a gray band composed of homogenous grayish lines (Fig 4). Some authors prefer touse the termmelanotic macule of the nail for this entity. 17 There are multiple causes for epithelial hyperpigmentation and their corresponding dermoscopic findings are listed below. Histopathology of these entities shows a normal number of melanin-containing melanocytes, which is approximately 6.5 cell/mm of the basal layer length. 18,19 Fig 1. Subungual hematoma. A, Clinical image. B, Der- moscopic image showing homogenous brownish to red- dish pigmentation without evidence of melanin inclusions. Lack of melanin inclusions suggests that the condition is caused by a nonmelanocytic lesion that has resulted in nail hyperchromia. It is also common in subungual hem- orrhage to see multiple reddish globules at the lateral and proximal edge of the pigmented area. In addition, one can see streaklike pigment at distal portion of pigmented area. Table I. The most frequent causes for longitudinal melanonychia Focal melanocytic activation Drug- and radiation-induced LM Endocrine LM LM associated with HIV infection LM associated with inflammatory nail disorders Laugier Hunziker syndrome Nonmelanocytic nail tumors Nutritional LM Traumatic LM Ethnic (racial) LM Systemic lupus erythermatosus Scleroderma Melanocytic hyperplasia Nevi of the nail matrix Melanoma of the nail matrix Other, less common causes LM, Longitudinal melanonychia. J AM ACAD DERMATOL VOLUME 56, NUMBER 5 Braun et al 837 Longitudinal melanonychia as a result of focal melanocytic activation: Drug- and radiation- induced longitudinal melanonychia. On clinical ex- amination, drug- and radiation-induced longitudinal melanonychia can be seen as horizontal or longitu- dinal bands or as diffuse nail darkening. It may affect the nails of the hands and feet and it can involve one or more digits. 19 Hyperpigmentation of the nail can also be associated with a hyperpigmentation of the skin. Dermoscopically homogenous grayish bands composed of gray lines can be observed. It has been reported to occur during or after treatment with some drugs, chemotherapy, or radiation therapy. This type of nail pigmentation is more commonly seen in individuals with phototypes IV, V, and VI skin than in individuals with fair skin. It usually appears 1 to 2 months after the beginning of the offending agent. For example, it is estimated that 67% of patients receiving AZT for the treatment of HIV Fig 2. Fungal infection with Trichophyton rubrum. A, Clinical image. B, Dermoscopy reveals a homogenous brown to black pigmented band that is devoid of visible melanin inclusions thus helping to correctly identify hyperchromia to be of nonmelanocytic origin. Fig 3. Dermoscopy of nail plate reveals, under high magnication, tiny granules that correspond to melanin inclusions. This feature suggests that the band is of melanocytic origin. Fig 4. Lentigo of the nail matrix. A, Clinical image. B, Dermoscopy shows parallel homogenous grayish lines that are juxtaposed to each other resulting in appearance of homogenous gray pigmented band. The band does have melanin inclusions that identifies it to be of melano- cytic origin. However, gray color suggests that the diag- nosis of this nail pigmentation is a result of epithelial hyperpigmentation, which is occurring in the absence of an accompanying melanocytic proliferation. J AM ACAD DERMATOL MAY 2007 838 Braun et al infection will develop this form of nail pigmentation. AZT-induced nail pigmentation usually develops be- tween 8 weeks and 1 year after the beginning of the therapy. 20 After the treatment is completed, the pig- mentation will progressively fade over several months but it may never completely disappear. Endocrine longitudinal melanonychia. Nail pig- mentation is a common feature of Addisons disease (diffuse pigmentation and/or LM). It may also be seen in Cushings syndrome, after adrenalectomy, 21,22 hyperthyroidism, 23 acromegaly, and during preg- nancy. 19 The clinical and dermoscopy findings are very similar to drug- and radiation-induced longitu- dinal melanonychia. Endocrine longitudinal melano- nychia mayaffect multipledigits. InAddisons disease, longitudinal melanonychia is typically associatedwith cutaneous and mucosal hyperpigmentation. Longitudinal melanonychia associated with HIV infection. In patients who are HIV positive, nail pigmentation unrelated to AZT treatment has been described. 24-26 The nail pigmentation usually affects multiple nails and is associated with pigmented mac- ules of the palms, soles, and mucous membranes. In most reported cases the patients died within months after the pigmentation appeared. Longitudinal melanonychia associated with in- ammatory nail disorders. This type of nail pig- mentation occasionally develops in nails affected by lichen planus, 27-29 onychomycosis, 12 chronic radiodermatitis, pustular psoriasis, or Hallopeaus disease. The pigmentation can be subtle at the beginning and become clearly clinically evident as the inflammatory process progresses. It is usually associated with nail scarring and abnormalities of the surface of the nail plate. The clinical and dermo- scopy aspect of this entity is not specific. Laugier Hunziker syndrome. Laugier Hunziker syndrome is an acquired disorder of the pigment system. The characteristic ndings include longitu- dinal melanonychia, and macular pigmentation of the lips, mouth, and anogenital area. 5,8 The nail pigmentation may appear either as a single or double band with a diameter between 1 to 2 mm or as homogeneous pigmentation of the lateral nail plate. Although the entire nail can become hyperpig- mented, this is rather rare. This form of pigmentation can be associated with a pseudo-Hutchinsons sign. Longitudinal melanonychia as a result of nonmelanocytic nail tumors. In rare cases non- melanocytic nail tumors can activate melanocytes resulting in the formation of a longitudinal pig- mented nail band. This entity is most commonly seen in association with Bowens disease. 30,31 Any longitudinal melanonychia in the presence of a nonmelanocytic tumor requires biopsy. Nutritional longitudinal melanonychia. Pig- mentation of the nails and the skin can be seen in vitamin B12 or folate deciency. 32,33 The pigmenta- tion tends to have a bluish-black color. The pigmen- tation on the skin is accentuated over the knuckles and the distal phalanges. Usually the diagnosis is made based on laboratory examination. This type of nail pigmentation is completely reversible after vita- min B12 or folate administration. Traumatic longitudinal melanonychia. Re- peated trauma such as nail biting may induce nail pigmentation. This is predominantly seen after re- peated minor trauma such as picking, chewing, breaking, or rubbing 34,35 of the proximal nailfold. This entity is usually associated with visible abnor- malities of the surface of the nail plate as a result of the repetitive nail matrix injuries. Frictional longitudinal melanonychia is mainly seen on the toes and is often associated with foot deformities, unsatisfactory footwear, or both. 36 This type of nail pigmentation may gradually fade once the repetitive trauma has subsided. Ethnic nail pigmentation. Ethnic or racial nail pigmentations are physiological longitudinal pig- mentations of the nail or nails observed in dark- skinned individuals with skin type V and VI. 37,38 They can present as single or more often multiple bands involving one or more digits. Systemic lupus erythematosus and scleroderma. Longitudinal melanonychia has been reported in Fig 5. Algorithm for dermoscopy diagnosis of nail pig- mentation that is of melanocytic origin. 1,12 In the first step, pigmentation should be evaluated for its color. Grayish color is highly suggestive of focal melanocytic activation in the absence of any melanocytic hyperplasia. Brownish color is suggestive for melanocytic hyperplasia. For the latter, lesions should be evaluated further to determine whether the pigmented lines comprising the band are regular, thus suggesting diagnosis of nevus or irregular suggesting possibility of melanoma. J AM ACAD DERMATOL VOLUME 56, NUMBER 5 Braun et al 839 rare cases of systemic lupus erythematosus 39 and scleroderma. 40 Nail pigmentation as a result of melanocytic proliferation. The term melanocyte hyperplasia should be reserved only for cases in which there is an increased number of melanin-containing melano- cytes ([6.5 cell/mm of basal membrane length) withinthe basal andsuprabasal layer. 18 It is important to remember that the architecture of the nail matrix together with the dendritic morphology and the suprabasal location of the nail matrix melanocytes can histologically simulate an in situ melanoma. Therefore, it is often difficult to differentiate between melanocytic hyperplasia and an in situ melanoma based on a partial biopsy specimen (ie, punch biopsy specimen) of the nail matrix. Whenever possible it is preferable to perform a complete longitudinal exci- sion of the band and submit it to the pathologist. Clinically longitudinal melanonychia appears as a single dark pigmented band. Dermoscopically the brown background pig- mented band is composed of multiple thin lines 1,10 (Fig 5). Depending on the dermoscopy pattern Fig 6. Nevus of nail matrix. A, Clinical image. B, Dermo- scopy reveals melanin inclusions that correctly identifies lesion to be of melanocytic origin. Thin lines within nail band have regular pattern, are parallel to each other, and have uniform thickness and spacing, all of which helps to correctly diagnose this as a benign nevus. Fig 7. Heavily pigmented nevus of nail matrix. A, Clinical image revealing pseudo-Hutchinsons sign that results from pigment in matrix becoming visible through rela- tively translucent cuticule. B, Dermoscopy shows melanin inclusions and regular dermoscopy pattern. J AM ACAD DERMATOL MAY 2007 840 Braun et al (regular or irregular) the following diagnoses should be considered. Regular dermoscopy pattern: Nevi of the nail matrix. Nail matrix nevi may be congenital or ac- quired and are often seen in children and young adults. Clinically they appear as longitudinal parallel and homogenous pigmentation of the nail. Its color varies fromlight brown (Fig 6) to dark brown to black (Fig 7). Usually nevi of the nail matrix are heavily pigmented and can clinically simulate melanoma. A pseudo-Hutchinson sign in which one can see the nail matrix pigment through a translucent cuticula is very common in nevi of the nail matrix (Fig 7). The most common conditions that can be associated with a pseudo-Hutschinsons sign are listed in Table II. Before dermoscopy the standard of care for many cases of melanonychia striata was excisional biopsy and histopathologic examination. However, because the dermoscopic criteria for nail pigmentation have now been well dened many cases can be managed without biopsy. Dermoscopically, nevi of the nail matrix show brown longitudinal parallel lines with regular spacing and thickness. This has been de- scribed as regular pattern. 1,10 Histopathology shows nests of melanocytes at the dermoepidermal junction. Junctional nevi are more frequently found than compound nevi. In general, nail matrix nevi occur more often on ngernails than on toenails. Irregular dermoscopy pattern: Melanoma of the nail matrix. Nail matrix melanoma has the same incidence across all races. However, they are the most frequent melanoma subtype in black and Asian populations. It usually affects middle-aged or elderly individuals. Nail matrix melanoma affects both n- gernails and toenails and is most frequently found on the index nger, the thumb, the large toe, or all of them. 41 Approximately 50% of patients with nail melanoma recollect preceding trauma. 1,2,41-43 A melanoma of the nail matrix usually presents as a broad band, dark brown to black in color with rather fuzzy or blurred lateral borders (Fig 8). However, it is not uncommon to encounter subun- gual melanoma with a light brown and thin band (Fig 9). In melanomas that are growing rapidly the lines within the band are not parallel and the diam- eter of the entire band is wider at the proximal end (Fig 10). In advanced stages dystrophy of the nail plate or even loss of the nail plate can be observed (Figs 11 and 12). This is a direct result of the progressive destruction of the nail matrix by the expanding tumor. Pigmentation of the nailfold cuti- cle and the surrounding skin, known as Hutchinsons sign, can frequently be observed (Fig 13). On dermoscopic examination, a nail matrix mel- anoma is characterized by the presence of brown background coloration of the band. However, the individual lines forming the band are irregular Fig 8. Melanoma of nail matrix. A, Clinical image. B, Dermoscopy shows melanin inclusions, brown to black color, and irregular dermoscopy pattern with longitudinal brown to black lines with variable spacing and thickness. In addition, parallel line pattern is disrupted, which is called disruption of parallelism. Table II. Conditions that may produce a pseudo-Hutchinsons sign Addisons disease AIDS Bowens disease Drug-induced pigmentation Laugiers syndrome Malnutrition Nail matrix nevi (heavily pigmented) Peutz-Jeghers syndrome Racial pigmentations (phototypes V and VI) Radiation therapy Trauma J AM ACAD DERMATOL VOLUME 56, NUMBER 5 Braun et al 841 (irregular pattern). Irregular lines tend to have dif- ferent degrees of pigmentation, varying thicknesses and spacing 1 (Figs 8 to 10). In some areas they might end abruptly and in others their parallelism is dis- rupted. Blood spots can also be found in melanoma and, thus, their presence does not automatically suggest the diagnosis of a subungual hemorrhage. The prognosis of nail matrix melanoma is generally worse than for melanoma in other sites. 44 This may, in great part, be because of delays in diagnosis. We have the impression that nail matrix melanoma will lend itself well to sentinel node biopsy, however, there is currently no literature available addressing this issue. 45 WHICH LESIONS SHOULD BE BIOPSIED? Any lesion with an irregular dermoscopy pattern should be biopsied. Independent from the morphology seen under dermoscopy the following situations should alert the physician to the possibility of malignancy 14,19 : 1. Isolated pigmented band on a single digit that develops during the fourth to sixth decade of life. Although melanoma can be seen in children it is a very rare event. 2. Nail pigmentation that develops abruptly in a previously normal nail plate. 3. Pigmentation that suddenly becomes darker or larger or when the pigment becomes blurred near the nail matrix. 4. Acquired pigmentation of the thumb, index fin- ger, or large toe. Fig 9. Melanoma of nail matrix. A, Clinical image. B, Dermoscopy shows melanin inclusions, brown lines with irregular dermoscopy pattern in which lines have varia- bility in thickness, color, and spacing. In addition, there is one line that disrupts normal parallelism. Fig 10. Melanoma of nail matrix. A, Clinical image shows that diameter of band is wider at proximal end as compared with distal end. This usually occurs in rapidly growing lesions. B, Dermoscopy reveals melanin inclu- sions at periphery of lesion, brown to black color, which suggests melanocytic proliferation, and irregular dermo- scopy pattern with variability in line pigment, thickness, and spacing. Parallelism is also disrupted. J AM ACAD DERMATOL MAY 2007 842 Braun et al 5. Pigment that develops after a history of digital trauma 41 and in which subungual hematoma has been ruled out. 6. Any acquired lesion in patients with a personal history of melanoma. 7. If the pigmentation is associated with nail dys- trophy including partial nail destruction or ab- sence of the nail plate (Figs 11 and 12). 8. If pigmentation of the periungual skin (including lateral nail folds) is found to be present (Hutch- insons sign) (Fig 13). This includes pigment of the cuticle or hyponychium. Although we fully agree with most of the conclu- sions made by Husain et al, 17 our opinions differ on the importance of dermoscopy. Besides the 8 points mentioned, we are of the opinion that dermoscopy can greatly assist in the management decisions regarding nail pigmentations. BIOPSY TECHNIQUES FOR NAIL PIGMENTATION The choice of the biopsy technique for longitudi- nal melanonychia depends on many factors such as location, degree of suspicion, 14,19,46,47 and: d Presence of periungual pigmentation or Hutch- insons sign (Fig 13). d Location of the band within the nail. d Origin of the band in the matrix. In other words, is the origin of the pigment in the proximal or distal nail matrix? d Width of the band. 1. Periungual pigmentation or pigmentation of the nailfold should be viewed as a sign of malignancy unless proven otherwise (Fig 13). If there are no other factors to account for this pigmentation, an adequate biopsy specimen, Fig 12. Amelanotic melanoma of nail matrix associated with complete nail dystrophy. Fig 13. Melanoma of nail matrix. A, Clinical image with pigment noted on nailfold, surrounding skin and hypo- nychium (Hutchinsons sign). B, Dermoscopy shows dif- fuse pigmentation with variable shades of brown; feature commonly seen in acral melanoma. Fig 11. Melanoma of nail matrix with destruction of the nail plate. J AM ACAD DERMATOL VOLUME 56, NUMBER 5 Braun et al 843 sometimes requiring en bloc excision down to the bone, is necessary to rule out melanoma. 2. When the lateral third of the nail plate is in- volved, then a lateral longitudinal excisional biopsy specimen will provide adequate tissue for the pathologist while giving the best chance for a reasonable cosmetic outcome (Fig 14, C). The incision should begin in the lateral nail groove and should reach a depth close to the underlying bone. The incision should extend the entire length of the lateral nail margin and should include 3 to 4 mm of the nail plate. This ensures that a full-thickness specimen of the nail bed and the nail matrix with its lateral horn is obtained. The excision should extend from the just below the distal interphalangeal joint to the hyponych- ium. Slightly curved scissors or a surgical blade are useful for separating the tissue from the bone. It is preferred that this separating process should begin at the distal (hyponychium) and proceed proximally toward the nail matrix while always maintaining contact with the bone. Sutures are placed on the proximal nailfold and the hypo- nychium. The lateral nailfold is sutured to the nail plate with the nail equivalent of a half-burried (in plate) horizontal matress suture so as to recon- struct the lateral nailfold. 3. When the mid portion of the nail plate is in- volved, the potential risk of postoperative nail dystrophy is high. Most of the nail pigmentations have their origin in the distal nail matrix, but to choose the optimal biopsy method, it is neces- sary to determine the origin of the melanocytes responsible for the nail pigmentation. This infor- mation may be obtained by sampling the free edge of the nail plate and using a Fontana- Masson stain as described previously. However, dermoscopy can also be helpful in such cases. By placing the dermoscope against the free edge of the nail it may be possible to determine whether the pigment is located in the upper part or the lower part of the nail plate as was described previously. 13 This noninvasive approach can provide the desired information instantaneously, often obviating the need for a nail clipping. Pigment localized to the lower nail plate reflects the presence of melanocytes in the distal nail matrix. For the best cosmetic outcome, the bi- opsy should only involve the distal matrix and the proximal matrix should be preserved as much as possible. In contrast, pigment localized in the upper nail plate reflects melanocyte activ- ity in the proximal nail matrix. In this scenario the biopsy specimen must include the proximal nail matrix and, thus, the risk of scarring and nail dystrophy after excision is unavoidable. The ultimate biopsy method decided on may also depend on the width of the longitudinal melanonychia. 14,19,46,47 d A double punch biopsy is recommended for a pigmented band that is less than 3 mm in diam- eter (Fig 14, A). The first and larger punch, usually 6 mm, removes a circular defect in the nail plate. The second and smaller punch, usually 3 to 4 mm, biopsies the nail matrix through the circular nail plate defect created by the first and larger punch. The first 6-mm nail disk is then put back into its originating place and serves as a dressing and allows for quicker wound healing. d For a pigmented band with a diameter of 3 to 6 mm and in which the pigment is found to arise from the distal nail matrix, a transverse matrix biopsy is recommended (Fig 14, B). However, if the pigment is found to arise from the proximal nail matrix then an en bloc removal and repair using a U flap is required (Fig 14, D). Transverse matrix biopsy: when performing a nail matrix biopsy it is important to try and main- tain the distal curvature of lunula. To provide access to the nail matrix necessitates the need for two small oblique incisions to be made on each side of the proximal nailfold. The fold is then retracted to expose the matrix. The proximal third Fig 14. Different biopsy techniques (after Haneke, with permission). A, Punch biopsy of nail matrix, which can be used for pigmented bands that are less than 3 mm in diameter. B, Transverse biopsy of distal nail matrix, which can be used for pigmented bands occurring in middle of nail plate and having diameter of between 3 and 6 mm. C, Longitudinal nail biopsy, which can be used to biopsy lateral nail pigmented lesions. D, Median longitudinal nail biopsy withUflap, whichcanbe usedtobiopsy mediannail pigmentation resulting fromlesions originating in proximal nail matrix and have diameter between 3 and 6 mm. J AM ACAD DERMATOL MAY 2007 844 Braun et al of the nail plate is then dissected and separated from the nail bed while the distal two thirds of the nail plate remains pristine and attached to the nail bed. This will insure that the distal rosette appear- ance of the nail bed is preserved. The specimen is then removed by a fusiform-shaped wedge with the convex portion of the crescent matching the contour of the lunula (Fig 14, B). The incision should extend to the level of the bone. The subsequent repair requires that the surrounding matrix be undermined so as to allow for primary closure. The closure can be accomplished by using interrupted stitches using a monofilament synthetic absorbable suture material (p.e. PDS 6.0). If care is taken and the proximal nail matrix is not disturbed the transverse biopsy will merely result inthinning of the involvednail plate but will not leave a permanent fissure as would result from a central longitudinal biopsy. Recently, tangential matrix excision has been suggested (Fig 15). This technique is similar to the transverse matrix biopsy but provides a specimen that is less than 1-mm thick. However, this technique may lower the risk of postoperative nail dystrophy. Obviously if the lesion is diagnosed as malignant, more extensive surgery is mandated. Scherenbergs releasing U-ap method: This method requires a rectangular bloc excision of the involved nail plate, nail bed, nail matrix, and prox- imal nailfold. The ap is created by a curved incision running along the lateral wall and extending from the distal end of the incision to the proximal edge of the matrix (Fig 14, D). The nail bed and matrix are separated from the underlying bone so as to provide complete mobility. The flap is then rotated into position and closed with 5-0 nylon sutures. The defect created in the lateral wall is allowed to heal by secondary intention. Efforts should be taken to keep the matrix from adhering to the overlying proximal nailfold so as to reduce the risk of adhesion and postoperative nail splitting. A modified technique has been described by Haneke 2 : a rectangular exci- sion that includes all of the affected tissue is removed en bloc. A flap, which includes 3 to 4 mm of the lateral nail wall, is raised by a curved incision that runs parallel to the excised rectangle and extends from the proximal edge of the matrix to just short of the distal edge of the excised tissue. This will then provide a bridge that will enhance the viability of the flap and facilitate its subsequent rotation. The rotated flap is then approximated to the remaining nail. The defect created by rotating the flap is allowed to heal by secondary intention. This technique enables the removal of the proximal portionof the nail matrix and results in acceptable postoperative changes in the nail apparatus. The resulting nail plate is diminished in its width but is otherwise normal except for a slight longitudinal ridge. However, despite meticulous sur- gical techniques and care it is sometimes impossible to avoid postoperative nail splitting. For pigmented bands greater than 6 mm in diam- eter, a matrix punch or transverse biopsy are usually adequate biopsy techniques that can be used during the preliminary investigation process (Fig 14, A). SURGICAL MANAGEMENT OF MELANOMAS OF THE NAIL APPARATUS Melanoma in situ The surgical treatment of an in situ melanoma requires the complete surgical removal of the nail apparatus including nail plate, nail bed, and nail matrix. The resulting defect can be repaired either with a split- or full-thickness skin graft. 48-52 Although it is possible to allow wound healing by secondary intention, this will often result in a surface that is not smooth and can have spicules of keratinizing tissue and, thus, is not as comfortable for the patient as the results obtained with a skin graft. Invasive melanomas The treatment of invasive melanoma of the nail unit often requires amputation of the effected digit. The choice between simple distal amputation of a Fig 15. Schematic showing technique of matrix shave biopsy (from Haneke, 2 with permission). LM, Longitudinal melanonychia; NP, nail plate; RNP, reflected NP; RPNF, reflected proximal nailfold. J AM ACAD DERMATOL VOLUME 56, NUMBER 5 Braun et al 845 portion of the digit versus more aggressive and extensive surgical procedures is dictated, to some extent, by the thickness of the tumor. In addition, the relative functional importance of a given digit may also inuence the extent of surgery. For example, if the melanoma is located on the large toe it is important, if at all possible, to preserve the proximal phalange because this is the insertion site for many muscles and is important for balance. Melanomas located on the thumb also require special surgical consideration. The thumb is the most important digit because it is the only one that is fully opposable to the tips of the ngers and gives us the ability to grasp and hold objects. Thus, needless to say, the level at which the amputation is performed has major implications for the dexterity of the involved hand. In summary, the primary priority regarding melanoma remains the complete surgical removal of the tumor followed by attempts to preserve functionality. Lastly, one needs to take the aesthetics into consideration. 48-51,53 CONCLUSION Longitudinal nail pigmentation occurs frequently enough that every dermatologist will be confronted with this condition in his or her practice. The differential diagnosis is fairly broad and includes entities listed in Table I. Each one of these conditions poses particular management issues. The use of dermoscopy can assist in the evaluation and possible diagnosis of nail pigmentation. It should be per- formed to help identify the type of pigment and to determine the origin of the pigment. This informa- tion in turn will help determine the most appropriate biopsy technique to use so as to provide maximal information while attempting to maintain cosmesis. It has been our experience that dermoscopy has greatly impacted our management decisions and has clearly reduced the number of unnecessary opera- tions performed on banal nail pigmented bands. 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